Tumor necrosis factor and the p55TNF receptor are required for optimal development of the marginal sinus and for migration of follicular dendritic cell precursors into splenic follicles
Tumor necrosis factor and the p55TNF receptor are required for optimal development of the marginal sinus and for migration of follicular dendritic cell precursors into splenic follicles
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DOI：
10.1006/cimm.2000.1636
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发表时间：
2000-04-10
影响因子：
4.3
通讯作者：
Kollias, G
中科院分区：
文献类型：
--
作者：
Pasparakis, M;Kousteni, S;Kollias, G
次级淋巴组织的发育和功能需要肿瘤坏死因子和淋巴毒素的信号传导。 LT beta R 缺陷的小鼠表现出淋巴结和派尔氏集结器官发生缺陷以及脾结构严重紊乱。相反，TNF或p55TNF-R缺陷不影响外周淋巴器官的器官发生，但干扰B细胞滤泡的形成以及所有次级淋巴器官中FDC网络和生发中心的出现。基于这些差异，我们之前假设 TNF 在淋巴结构中的作用与 LT 的作用不同，并且在调节细胞相互作用方面受到限制，从而允许 FDC 的分化和/或正确定位。在本研究中，我们发现，除了滤泡结构的缺陷之外，TNF 或 p55TNF-R 敲除小鼠在巨噬细胞群和脾边缘区窦内衬细胞的形成方面也表现出缺陷。有趣的是，大量用 FDC 特异性标记物染色并能够捕获免疫复合物的树突状细胞保留在 TNF 和 p55TNF-R 敲除脾脏的缺陷边缘区内。我们得出的结论是，TNF 或 p55TNF-R 敲除小鼠的淋巴表型的主要缺陷是 FDC 前体无法迁移通过杂乱的边缘窦并正确归巢到脾滤泡区域，在那里它们将促进 B 细胞滤泡和生发中心的形成。 (C) 2000 年学术出版社。
The development and function of secondary lymphoid tissue require signaling by tumor necrosis factor and lymphotoxins. Mice deficient in LT beta R show defective organogenesis of lymph nodes and Peyer's patches and a severely disturbed splenic architecture. In contrast, TNF or p55TNF-R deficiency does not affect the organogenesis of peripheral lymphoid organs but interferes with the formation of B cell follicles and the appearance of FDC networks and germinal centers in all secondary lymphoid organs. Based on these differences, we have previously hypothesized that the role of TNF in lymphoid structure is distinct from that of LT and restricted in regulating cellular interactions that allow the differentiation and/or correct positioning of FDCs. In the present study we show that, in addition to the defects in follicular structure, TNF or p55TNF-R knockout mice exhibit defects in the formation of the macrophage populations and of the sinus lining cells of the splenic marginal zone. Interestingly, a large number of dendritic-shaped cells stained with FDC-specific markers and able to trap immune complexes are retained within the defective marginal zone of TNF and p55TNF-R knockout spleens. We conclude that the primary defect in the lymphoid phenotype of TNF or p55TNF-R knockout mice is the failure of FDC precursors to migrate through the disorganized marginal sinus and to home properly into the splenic follicular areas where they would promote the formation of B cell follicles and germinal centers. (C) 2000 Academic Press.